Drug research strives to increase the physiological relevancy of experimental models in early discovery, e. g. by using material from human donors for HCS. Using such physiologically relevant cell models can however introduce challenges due to the limited amount of material available for experimentation and the variation between donors.

In this poster, we show how our recently introduced Deep Learning-based high content analysis software remedies this situation by successfully transferring knowledge obtained from previous experiments to a new experimental...

The notion of morphologically different ‘cellular phenotypes’ lies at the core of high-content screening (HCS). Robustly differentiating these phenotypes is key to obtaining reliable quantitative information from high content screens. Such phenotypes serve: (1) as stable endpoints for primary drug response, (2) for assessment of toxicity and safety-relevant effects, (3) for the discovery of previously unexpected drug effects. However, a cellular phenotype to-date is defined by an agreement between experts about what visual aspects define it. So far, the...

The insight into the heterogeneity of cancers brought the need in oncology to extensively profile drugs and candidates for their bioactivity across many targets and representative cell lines. Such testing would identify more specific and potent molecules for targeted cancer treatment and refined cause-activity relationships by linking phenotypic effects to molecular markers. However, the related experimental effort is quite high, both in terms of assay complexity and number of tests required, since these tests are performed on panels of hundreds of...

We have implemented a dedicated end-to-end platform to support the whole bioprocess development workflow. Co-developed in close collaboration with leading biopharmaceutical companies, the platform fully automates the cell line and scale-down upstream process assessment. In addition, the system manages upscaling, downstream process, analytical and formulation development, which enables the lineage tracking of all batches, starting from the transfection of a cell line all the way to the vials containing the final drug product. Analytical data, as well as...

TCRs, antibody TCR-mimetics, CARs can provide significant advantages over traditional mAb approaches for the treatment of cancer. However, as highly engineered entities, they pose new design, cloning, expression, purification, and analytics challenges. Our workflow platform, employed by top biopharma companies, enables the automation, engineering, production, and testing of large panels of these candidate therapeutic molecules. We demonstrate the platform’s high-throughput capability when handling novel molecule-specific designs and its built-in tools...

Monitoring of critical quality attributes (CQAs) is currently performed using an array of analytical techniques. Many industrial players in biotherapeutics are exploring the adoption of innovative analytical approaches employing mass spectrometry (MS) to enable direct measurement of CQAs at the molecular level. In addition, MS-based methodologies offer the benefit of measuring many different quality attributes of a given biotherapeutic with a single test. These multi-attribute methods (MAMs) can potentially reduce development and manufacturing costs and...

Mass spectrometry is a key technology for characterizing biotherapeutic candidates throughout the discovery, development, and manufacturing cycle. Here we present Genedata Expressionist®, an enterprise software system that enables organizations to streamline and share their mass spectrometry data analysis and management processes company-wide.

Allowing unbiased identification and high throughput quantification of multiple low-abundant proteins, mass spectrometry (MS) is proving to be the ideal analytical platform to provide a thorough assessment of host cell proteins (HCPs) in biotherapeutics.However, the use of MS for HCP analysis also poses some challenges:

HCP contaminations can span a wide range of on centrations, with low abundant species present at the ppm level;

a number of analytical approaches are currently being explored, however no standardized methods are available yet;

Complete characterization of large and complex drug candidates remains a challenging task. Scientists are asked to report not only the main components, but also traces of truncated or modified versions of the drug candidate. Intact mass analysis is a key analytical assay for the identification and relative quantification of large molecules in a sample.

Monitoring of critical quality attributes (CQAs) is currently performed using an array of analytical techniques. Many industrial players in biotherapeutics are exploring the adoption of innovative analytical approaches employing mass spectrometry (MS) to enable direct measurement of CQAs at the molecular level. In addition, MS-based methodologies offer the benefit of measuring many different quality attributes of a given biotherapeutic with a single test. These multi-attribute methods (MAMs) can potentially reduce development and manufacturing costs...

Mass spectrometry is a key technology for characterizing biotherapeutic candidates throughout the discovery, development, and manufacturing cycle. Here we present Genedata Expressionist®, an enterprise software system that enables organizations to streamline and share their mass spectrometry data analysis and management processes company-wide.

We present an innovative workflow based on convolutional neural networks (‘Deep Learning’), providing life science research with more relevant information from today’s imaging technologies and increasing throughput (the principles of deep learning in HCS have recently been shown, e.g. by [1-2]). The workflow is tailored towards pharma-relevant assays, minimizing the need for expert time and knowledge, both during assay development and production. It aims to support complex research situations such as the phenotypic in-vitro assays that are highly...

With the decreased cost of next generation sequencing (NGS) technologies, full genome sequencing of production strains and derivatives has become routine. The management and analysis of strain sequence, variant, and expression data is challenging due to a lack of integrated computational solutions that support workflows from raw next generation sequencing data to biological insight.

Genome editing techniques such as the CRISPR/Cas9 system are transforming molecular biology and equipping scientists with the ability to precisely modify the DNA of virtually any organism. Industries from biopharmaceutical to industrial biotech to food and beverage are utilizing this RNA-guided nuclease based approach for its versatility, ease of use, reliability, and efficiency to perform different experiments such as strain optimization or cell line design. From a bioinformatics perspective,...

Outsourcing of screening can pose massive challenges to pharmaceutical research organizations. Experimental procedures, research processes and results that have painstakingly been standardized and perfected over years are now placed in the hands of contract research organizations (CROs) or other collaboration partners. This creates uncertainty regarding source, quality, and significance of results. It can lead to mismatches with internal experimental procedures and research processes when only parts of the screening are...

Since the introduction of the drug-target residence time model 10 years ago (1,2), binding kinetics have become an important enhancement to “classical” drug discovery metrics (such as potency) when it comes to making compound progression and candidate selection decisions. This paradigm shift has been backed by retrospective analysis of recently approved drugs showing that nearly one third act via non-equilibrium mechanisms (3), and by studies suggesting that the incorporation of in-vitro kinetic information in drug discovery programs...

The development process for large-molecule therapeutics is a complex task. Biopharmaceutical drugs are made of large, complicated, and fragile biomolecules that are produced in highly complex manufacturing processes. Novel therapeutic classes such as bi- and multi-specific antibodies, ADCs, and novel scaffolds pose additional challenges in expression, purification, analytics, and formulation development. Here, we present a new workflow platform for large-molecule development and CMC, which has been designed to make biopharma development operations...

Over the past two years, a team has been developing a comprehensive Biotherapeutics Informatics platform to centralize the storage of information and data for sequences, potential liabilities, assays, inventory, and other project- and group-specific information. The platform — now in use across multiple groups and sites — is built around the Genedata Biologics commercial software package, which we have supplemented with Pfizerproprietary computational methodology and have integrated into Pfizer’s biotherapeutic R&D...

The discovery and development of large-molecule therapeutics is fundamentally different from the small-molecule, chemical R&D process. The design, production, and testing of innovative biopharmaceuticals produces huge volumes of complex data that need to be captured, structured, integrated, processed, analyzed, and interpreted. The management of such data generated along the biologics R&D process is one of the key bottlenecks in large-molecule R&D. Here, we present the Genedata Biopharma Platform, an enterprise software system that supports the...

The term adventitious agent generally describes bacteria, viruses, fungi, and other microorganisms that contaminate products produced using biotechnology. Current molecular methods for detecting adventitious agents require targeted probes for identification of small panels of known contaminants. Untargeted approaches like culture based assays require weeks to complete. NGS provides an untargeted and rapid method for identification of the nucleic acid content of all adventitious agents in a biological sample. A major challenge of using NGS...

With increased number of experiments performed in bioprocess development, the capturing, processing, aggregation, visualization, and statistical analysis of generated data has become a major bottleneck. Association of the data with the experimental context (e.g., fermentation protocols, media recipes, bioreactor control parameters) is also challenging in high throughput. New and highly performant data capture, rocessing, and analysis systems need to be integrated to enable processing of analytics data. We have developed a new platform for bioprocess...

The availability and quality of the tools being used for drug targets, other protein reagents, or cell lines represent important prerequisites for successful drug discovery and development projects. The tools are typically produced by cell and protein sciences or technology groups and are supplied to small-molecule and large-molecule research and screening as well as to structural biology and PKPD groups. Tool proteins and cell lines are usually applied in many types of bioassays and compound characterization, in high throughput screening, and in...

In the process of discovery and development of novel biologics as therapeutic agents a continuous assessment of their quality and developability is crucial. Therefore, more and more analytics methods are being applied on an increasing number of drug candidates in earlier stages of the biopharma R&D workflows. In parallel, data management systems are needed to help researchers keep track of the molecules, their samples, and their characteristics. The analytics parameters being tracked include not only biological data such as bioactivity, but also...

Bispecific antibodies (BsAbs) have traditionally been developed by first optimizing antibody fragments then reformatting to the final bispecific format at the engineering stage. However, studies have shown that this method misses effective BsAbs. Moreover, costly engineering efforts are wasted optimizing BsAbs that once assembled turn out to be non-functional, unstable, or kinetically unsuitable. This is leading to a paradigm shift in BsAbs development: screening in the final therapeutic format as early as possible (“in-format screening”). This approach...

We have implemented a dedicated end-to-end platform to support the whole bioprocess development workflow. Co-developed in close collaboration with leading biopharmaceutical companies, the platform fully automates the cell line and scale-down upstream process assessment. In addition, the system manages upscaling, downstream process, analytical and formulation development, which enables the lineage tracking of all batches, starting from the transfection of a cell line all the way to the vials containing the final drug product....

Automated patch clamp screens generate highly valuable information for drug research programs. In particular, in safety pharmacology early testing is nowadays seen as a cornerstone for managing risk of later failure and patients’ health. Thus, more predictive and affordable screens need to be introduced to gain both specificity and throughput e.g. for cardiovascular liability detection and resolution. At AstraZeneca, we have implemented the Nanion Syncropatch 384PE electrophysiology platform, delivering higher throughput measurements for hERG and...

Antibody Drug Conjugates (ADCs), or immunoconjugates, play an increasingly important role as a new class of oncology medicines which use the selectivity of monoclonal antibodies to achieve targeted delivery of cytotoxic drugs. However, the underlying ADC discovery and development process is complex and poses significant challenges in that systematic ADC design uses a combination of optimal conjugation strategy (e.g. lysines, cysteines, Fc glycans, non-natural amino acids), linkers (e.g. cleavable, non-cleavable), and small-molecule toxophores (e.g....

So much of the success of a drug discovery and development project depends on the availability and quality of tool proteins representing the drug targets and other protein reagents. The tool proteins typically produced by protein sciences and technology groups are supplied to small-molecule and large-molecule research groups, medicinal chemistry groups, and others, and are used for various purposes such as high-throughput screening, structural biology and crystallization studies, or antigen materials. Genedata Biologics™ is an established enterprise...

Presented at the Recent Advances in Microbial Control Conference, San Diego, CA, USA

With the decreased cost of next generation sequencing (NGS) technologies, metagenomics is now a common tool in biological research. The study of microbiome genomics is especially challenging due to a lack of integrated computational solutions that support workflows from raw next-generation sequencing data to biological insight.

As a comprehensive and scalable software platform, Genedata Selector directly addresses the complex challenge of NGS data analysis and management. The system offers an end-to-end...

Achieving the vision of precision medicine is reliant to a large degree on translational research activities that require researchers to characterize and profile patients in order to understand their response to new therapies, stratify patients for trials or search for new disease biomarkers. The process of translational and clinical research poses significant challenges for organizations, ranging from federation of large volumes of disparate genomic and phenotypic data, through generating meaningful conclusions from such...

Adding to current image-based screening activities such as Digital Pathology (DP) and High-Content Screening (HCS), new biomedical imaging technologies such as Mass Spectrometry Imaging (MCI) and various Single Plane Illumination Microscopy techniques are becoming commonplace in the field of preclinical drug discovery and development. These emerging technologies excel during the late Research & Development phases, allowing scientists to quantify drug efficacy, understand cellular mechanisms and drug mode of action, and study system-level...

Peptide mapping is an essential analytical technique for characterizing the primary structure of protein-based therapeutics. In bioprocess development, for instance, peptide maps are employed for lot-to-lot identity testing. Likewise, peptide mapping is considered a vital step in comparing an innovator and a biosimilar. Recent developments in separation techniques, MS instrumentation, and sample preparation procedures have allowed scientists to implement peptide mapping in their routine biotherapeutics characterization pipelines. While...

Biotherapeutics candidates are selected not only for their biological activity, but also for their developability profile, a set of properties which give an indication of the risks and costs of technical development and manufacturing. A developability assessment performed at the beginning of the development phase is key to success, reducing the risk of investing resources on biomolecules that are difficult to develop or that pose huge technical challenges later, during formulation or production. The assessment is based on experimental...

The key aim of cell line development is the provision of stably expressing, high-yield mammalian cell lines for biopharmaceutical production. Recent progress in automation technologies, as well as new Quality-by-Design (QbD) approaches, have resulted in a very significant increase in experimental throughput. This, in turn, has led to a dramatic increase in the number of samples and associated analytics data that need to be processed, analyzed, interpreted, and reported across the whole CMC/Pharmaceutical Development organization. Here, we...

Analysis of image-based high content screens typically starts with automated image analysis followed by processing and analysis of the extracted numerical data. This data analysis workflow often consists of three canonical steps: a) ensuring result integrity through appropriate QC procedures and result comparability through data normalization, b) definition of the final activity or potency of individual compounds based on a single or a few HCS readouts, and c) generation of hit lists by simple filtering rules.

Breast and ovarian cancers pose huge and still largely unsolved challenges for the medical profession. Most women with screening-detected breast cancer do not receive a clear treatment benefit, indicating that these cancers are still not being detected early enough. The less common ovarian cancer is often not diagnosed until in an advanced stage, resulting in a five-year survival rate of less than 40%. New tests based on genomic biomarkers have the potential to offer, for the first time, much earlier detection and diagnosis of ovarian...

Biopharmaceuticals are the drugs of the future, but their generation, design, and engineering is complex and expensive. Gaining a better understanding of the factors behind the efficacy, expressibility, stability and immunogenicity of biopharmaceuticals is crucial to improve protein engineering and reduce development timelines and costs. Here we present a novel informatics platform for antibody screening, engineering, and production, that enables researchers to integrate and visualize sequence (CDR compositions, AA residue distribution, PTMs, etc.),...

In the process of discovery and development of novel biologics as therapeutic agents the early assessment of their quality and developability is crucial. Therefore, more and more analytics methods are being applied on an increasing number of drug candidates in earlier stages of the biopharma R&D workflows. In parallel, data management systems are needed to help researchers keep track of the molecules, their samples, and their characteristics. The analytics parameters being tracked include not only biological data such as bioactivity, but also physicochemical...

The discovery of monoclonal antibody drugs is a complex and costly exercise. Reducing product cycle time and improving the lead quality early in the R&D process is essential for successful development of new biotherapeutic drugs. This requires earlier and more detailed evaluation of increasingly large panels of biomolecules, derived from any display, hybridoma, or B cell technology.

The discovery and development of large molecule therapeutics is fundamentally different from the small molecule, chemical R&D process. Biomolecule registration requires comprehensive documentation of all development and production parameters along the R&D process, including cell lines, vectors, or expression and purification protocols. Here, we present a new registration platform, developed together with major biopharmas, which enables registration and tracking of all biologic molecules and samples. It can handle complex pools and mixtures, as well...

Presented at the Cell Line Development Conference 2016, Vienna, Austria

The introduction of next generation sequencing and omics technologies has changed the way in which cell line can be designed, selected and optimized. With the new era of genome-based cell line design, selection and gene editing, we have seen that there is an immediate need for seamless data management, integration, analysis, and result sharing. Furthermore, complex experimental workflows may require different tools and are only partially supported by currently available solutions. To address this need, we have developed...

Presented at the World Congress on Industrial Biotechnology, San Diego, CA, USA

The rapid evolution of Next Generation Sequencing (NGS) technologies has led to an explosion in the volume of data and the types of applications used in various business industries (e.g. agriculture, industrial biotechnology, biofuels, biopharma, food and beverage, and cosmetics). In order to get the full value of NGS and Omics data, bioinformatics tools for knowledge management, data storage, and analysis must address different workflows and provide the flexibility to integrate proprietary and public information...

Presented at the World Congress on Industrial Biotech, San Diego, CA, USA

With the decreased cost of next generation sequencing technologies (NGS), metagenomics is now within the reach of many labs and researchers. However until now, the study of microbiome genomics suffered from a lack of integrated computational solutions that allow to seamlessly go from raw next-generation sequencing data to the statistical analysis of results and metadata to the interactive visualizations that provide the insights. The comprehensive and scalable genome knowledge management suite, Genedata Selector,...

New strategies and technologies enable a systems biotechnology approach to decipher molecular mechanisms in the cell, and new approaches for the discovery and engineering of genes have significantly improved the ability to produce proteins which resist standard expression methods. For successfully expressing refractory proteins, strategies and methods include specialized engineering of genes/vectors/strains (e.g. focusing on the secretion apparatus), advanced molecular design, integration site determination, CNV and insert integrity analysis and focusing on...

In this poster we present an automated data processing and analysis approach for the determination of DAR. Noise removal and smoothing algorithms were combined with the deconvolution of intact mass spectra using the Maximum Entropy method. Our approach was applied to the comparison of two samples containing the same ADC but produced with two different processes. All operations were conducted using Genedata Expressionist® (Genedata AG, Basel, Switzerland) software.

New technologies have changed the way in which cell line development, cell line selection and cell culture R&D generally is performed. However, genomic and molecular data are often scattered in different locations. Additionally, data quality issues may be inadequately tracked, leading to suboptimal decisions and increasing the risk of project failure. To address these challenges, we developed an integrated knowledge management and data analysis platform, Genedata Selector™.

Image-based high content screens are mainly analyzed the following way: HCS images are subjected to automated image analysis using protocols defined in assay development, yielding numerical data on the object level, which are then averaged to the well level. After a quick-pass QC, the final activity or potency of individual compounds is typically determined based on one to three readout(s), which are often normalized, and hit lists are generated by simple filtering rules.

Identification and quantification of biopharmaceuticals using intact mass spectrometric analysis remains a challenging task. Conventional analysis results in incomplete characterization which is difficult to interpret. Genedata Expressionist® features a fully-automatable time-resolved LC-MS deconvolution algorithm, resulting in deeper understanding of the protein. Using the example of a human IgG-type antibody, reduced and subsequently digested by an IdeS enzyme, we demonstrate the accurate quantification of traces of partially reduced versions...

Genedata ProfilerTM is a new translational research software platform developed in collaboration with leading pharmaceutical companies to process, manage, and analyze NGS and other omics data from patient samples, applying highest data quality and regulatory compliance standards. Strict user management, audit trailing, access authorization, and a comprehensive reporting infrastructure are central components of the software to ensure conformity with the tightening legal framework governing clinical and pharmaceutical data privacy and security....

Mass spectrometry has rapidly become a key technology for the complete characterization of biotherapeutic candidates, a task that is required throughout the entire discovery, development, and manufacturing cycle. Many biopharmaceutical organizations strive to increase sample throughput and reproducibility of results by standardizing and automating data processing, analysis, and management. Automation, method synchronization and data access across projects and geographies, as well as flexible reporting, are...

Presented at ELRIG Drug Discovery, Telford, UKSurface Plasmon Resonance (SPR) is a powerful method for obtaining detailed molecular interaction parameters. Modern instrumentation with its increased throughput has enabled routine screening by SPR in hit-to-lead and lead characterization programs, moving SPR technology into the mainstream of drug discovery. However, the set-up of SPR data management and analysis typically still depends on the type of SPR instrument, and SPR results are manually transferred from the stand-alone instrument to the drug discovery workflow. To increase user...

Presented at the World Congress on Industrial Biotechnology, Montreal, Canada

Metagenomics has emerged as a powerful tool to analyze microbial communities regardless of the ability of member organisms to be cultured in the laboratory. With the decreased cost of next generation sequencing technologies (NGS), metagenomics is now within the reach of many labs and researchers. Combining NGS with advanced bioinformatics solutions provides researchers with an opportunity to taxonomically profile entire microbial communities, decipher structure and function of various microbes, and generate novel...

Presented at the World Congress on Industrial Biotechnology, Montreal, Canada

The rapid evolution of Next Generation Sequencing (NGS) technologies has led to an explosion in the volume of data and the types of applications used in various business industries (e.g. agriculture, industrial biotechnology, biofuels, biopharma, food and beverage, and cosmetics). In order to get the full value of NGS, bioinformatics tools for knowledge management, data storage, and analysis must address different workflows and provide the flexibility to integrate proprietary and public information in an open,...

New technologies have changed the way in which cell line engineering and cell culture R&D generally is performed. However, genomic and molecular data are often scattered in different locations and not easily accessible. Additionally, data quality issues may be inadequately tracked, leading to suboptimal decisions and increasing the risk of project failure. Complex workflows may require different tools or may not be supported by available solutions.To address these challenges, we developed a single, integrated knowledge management and analysis platform,...

To support the development of fully traceable, stable, and high-yielding cell lines and reduces development time, we have developed an integrated knowledge management platform, Genedata Selector. The system integrates varied public and proprietary “omics” data from different sources and is highly scalable, being able to handle hundreds of genomes and related information. Additionally, all publicly available CHO cell lines and the Chinese hamster genome with refined gene models, improved functional annotation, TFBS and pathway information are integrated in...

As the range of assays, instruments, and user groups increases, so does the complexity of the high content screening (HCS) infrastructure needed to support it. Complexity can be greatly reduced using a central hub for images and their associated results, providing data consistency and downstream access for other analysis tools. However, setting up a hub that complements all the existing workflows is challenging. Alternative solutions often involve a high degree of manual work (e.g., moving files manually from tool to tool) or script-controlled pipelines...

There is an increasing need for very high throughput methods to analyze and gate single-cell data, both for object-level data from HCS assays, and for working with results from new automated plate-based flow cytometry platforms. Existing software solutions are typically not capable of handling data in amounts greater than a single plate and lack methods that support basic screening concepts such as normalization, replicate analysis, and quality metrics.

Electrophysiological ion channel measurements generate a significant amount of signal data with time traces often consisting of hundreds or thousands of data points. Furthermore, multiple events must be inspected, analyzed, and combined for an optimal analysis result. This, together with high data volumes, makes data processing very time consuming and laborious. In addition, recent advances in automated electrophysiology enable the screening of thousands of compounds per week, but data handling/processing infrastructures have not kept pace with...

This poster shows the technological infrastructure and its application to HT-HCS at the Weizmann Wohl Institute for Drug Discovery. First, we illustrate the set-up of an academic small-molecule screening facility maintaining a diverse compound library of 100,000 molecules. The set-up comprises automated workstations and detection technologies for many biochemical and cell-based assays (fluorescence intensity, luminescence, TR-FRET, fluorescence polarization, automated microscopy for high-content...

This poster illustrates the utility and importance of a metric for ion channel modulation by compounds that is orthogonal to the commonly used percent activity calculated e.g. from peak current vs. control. In this example, we determine the (macroscopic) time constant (tau) of channel inactivation. In order to achieve a very fast analysis of results concomitant with routine high-throughput screening, we calculate tau by exponential decay functions. A recently developed APC assay on the IonFlux HT...

The use of hybridoma libraries is an established technology for the generation of successful therapeutic antibodies. Here, we present a new workflow management system that increases the throughput and efficiency of antibody screening, engineering, and production workflows. In particular, we discuss the challenges in supporting high-throughput hybridoma generation and screening workflows, subsequent chimerization and humanization of murine antibodies, and expression and analytical evaluation of murine and humanized constructs. These processes create new...

Surface Plasmon Resonance (SPR) is a powerful method for obtaining detailed molecular interaction parameters. It has had increasing impact in hit-to-lead and lead characterization programs and more recently in screening, leading to an explosion of the variety of SPR instruments available on the market.

However, data management and analysis capabilities fall short of enterprise needs. For example, each instrument typically comes with its own specialized analysis software, posing a major challenge to pharmaceutical companies and hampering the...

We present the development and implementation of an innovative turn-key MorphoSys solution which supports biopharma R&D workflow and data management, developed in collaboration with Genedata. We present the specific challenges encountered, including process complexity and new technology support. Examples cover processes from antibody library generation and screening to protein engineering, expression, purification, and analytics. YBase was built on the Genedata Biologics platform, utilizing a structured and agile...

Drug combination treatments have been widely recognized as an essential therapeutic strategy for chronic diseases such as cancer. A successful combination approach enhances clinical efficacy through drug synergistic effect, improved therapeutic window by reducing effective clinical dosage, and overcoming or delaying the onset of drug resistance.

In order to rapidly identify effective and disease-specific combinations across a large spectrum of drug candidates preclinically, in vitro cell-based phenotypic assays remain the most viable approach. However,...

This poster describes a standardized novel data QC- and analysis workflow for Thermofluor™ experiments. Compared to conventional procedures, this workflow represents a significant speed-up (from two days to two hours) of the evaluation and reporting of Thermofluor results with increased quality.

CaV2.2 channels regulate neurotransmitter release in neurons and play a critical role in pain signaling. It has been proposed that a state-dependent CaV2.2 inhibitor which preferentially binds to channels in open or inactivated states may improve the therapeutic window over relatively state-independent CaV2.2 inhibitors. We have developed a robust fluorescent-based functional assay to identify state-dependent CaV2.2 inhibitors.The novel assay design, coupled with an information-rich readout and sophisticated data analysis, led to a robust and reproducible...

The gastric pathogen Helicobacter pylori is responsible for gastric inflammation and the second highest number of infection-associated cancers. The transcription factor NFkB, a key mediator of host tissue inflammation, induces the expression of pro-inflammatory cytokines, which have been shown to be important for the development of gastric cancer. To better understand NFkB activation in response to H. pylori infection, a genome wide RNA interference screen was performed, resulting in 300 primary hits. To characterize the effects of these 300 hits a...